ACC is an enzyme that converts acetyl-CoA to malonyl-CoA, and catalyzes a rate determining reaction in fatty acid metabolism. Malonyl-CoA, which is produced by an ACC catalyst reaction, inhibits fatty acid oxidation in mitochondria based on the feedback inhibition of carnitine palmitoyl transferase-1 (CPT-1). Accordingly, ACC plays a key role in controlling the balance between use of carbohydrate and fatty acid in the liver and skeletal muscle, and further, controlling insulin sensitivity in the liver, skeletal muscle and adipose tissue.
A reduced level of malonyl-CoA by ACC inhibition can promote an increase in fatty acid oxidation, decreased secretion of triglyceride (TG)-rich lipoprotein (VLDL) in the liver, regulation of insulin secretion in the pancreas, and further, improvement in the insulin sensitivity in the liver, skeletal muscle and adipose tissue.
In addition, long-term administration of a compound having an ACC inhibitory action can strikingly decrease the TG content of the liver and adipose tissues and selectively decrease body fat in obese test subjects taking low fat diet, by promoting fatty acid oxidation and suppressing de novo synthesis of fatty acid.
Accordingly, a compound having an ACC inhibitory action is extremely useful for the prophylaxis or treatment of metabolic syndrome, obesity, hypertension, diabetes, cardiovascular diseases associated with atherosclerosis and the like.
On the other hand, the following compounds have been reported.    (1) A compound represented by the formula:
wherein    R1 is alkyl, aryl or the like,    R1′is a hydrogen atom, alkyl or the like,    R2, R3 and R4 are each independently a hydrogen atom, alkyl or the like,    Xa is optionally substituted cycloalkyl, optionally substituted heteroaryl (the heteroaryl may be optionally a fused ring or a spiro ring) and or like,    Y is linker such as alkylene, alkenylene or the like,    Z is N, and    n is an integer of 1 to 6,    (see Patent Document 1).    (2) A compound represented by the formula:
wherein    R1 is alkyl, aryl or the like,    R1a is a hydrogen atom, alkyl or the like,    Xa is
or the like,    R3 is a hydrogen atom, optionally substituted alkyl or the like,    R4 and R4a are each independently a hydrogen atom, alkyl or the like,    R6 is a hydrogen atom, alkyl or the like,    A is O, S, NH or the like,    Y is
                wherein        x and y are each independently an integer of 0 to 3, and z is an integer of 0 to 3, and            Xb is
    (see Patent Document 2).    (3) A compound represented by the formula:
wherein    R1, R2 and R3 are each independently a hydrogen atom, optionally substituted alkyl or the like,    A is optionally substituted aryl, heterocyclic group or cycloalkyl,    Y is
    R4 and R5 are each independently a hydrogen atom, optionally substituted alkyl, carboxyl group or the like,    R6 and R7 are each independently a hydrogen atom, halogen, —OH, —CN or the like,    R8 and R9 are each independently a hydrogen atom, optionally substituted alkyl or the like, and    R3-R9 optionally form an optionally substituted carbocycle or an optionally substituted heterocycle,    (see Patent Document 3).    (4) A compound represented by the formula:
wherein    R1 is a hydrogen atom, lower alkyl or the like,    R2 is a hydrogen atom, optionally substituted alkyl or the like,    R3 and R4 are each independently a hydrogen atom, lower alkyl,
or the like,    A3 is lower alkyl substituted by 5- to 14-membered heterocycle(s) (the heterocycle is optionally condensed),    R8 is a hydrogen atom, oxo, —CONR9R10 or the like, R9 and R10 are each independently a hydrogen atom, phenyl or the like,    n is 0,    m is 0 or 1, and    r is 1 or 2,    (see Patent Document 4).    (5) A compound represented by the formula:
wherein    T is a hydrogen atom, hydrocarbon, —F—R, or a bond to the one of D, E, P and Q, or form, together with the one of P and Q, a ring,    Z is an atom having valence m,    M is a valence of Z,    D, E and F are each independently a linker (when Z is N, E is neither CH2 nor CO), and    P, Q and R are each independently a ring (Q contains sulfamate group),    (see Patent Document 5).    (6) A compound represented by the formula:
wherein    E is an optionally substituted cyclic group (provided that the cyclic group is not a spiro ring group, and when the cyclic group is a monocyclic group, the cyclic group has at least two optionally substituted cyclic groups as substituents);    D and G are independently carbonyl group or sulfonyl group;    ring P is an optionally substituted nitrogen-containing 5- or 6-membered non-aromatic heterocycle,    ring Q is an optionally substituted aromatic ring or an optionally substituted non-aromatic heterocycle (provided that the non-aromatic heterocycle contains two or more hetero atoms);    A and L are independently C, CH or N; and    J is an optionally substituted hydrocarbon group, an optionally substituted hydroxy group, an optionally substituted heterocyclic group or an optionally substituted amino group,    (see Patent Document 6).    (7) A compound represented by the formula:
wherein    E is an optionally substituted cyclic group;    D is a carbonyl group or a sulfonyl group;    A is CH or N;    ring P is an optionally further substituted 5- to 7-membered ring;    ring Q is an optionally further substituted 5- to 7-membered non-aromatic ring; and    ring R is an optionally fused 5- to 7-membered non-aromatic ring which is optionally further substituted,    (see Patent Document 7).    (8) A compound represented by the formula:
wherein    ring M is a 5- or 6-membered aromatic ring;    W is C or N;    K is an optionally substituted methylene group or an optionally substituted imino group;    R is a hydrogen atom, an optionally substituted hydrocarbon group, an optionally substituted hydroxy group or an optionally substituted heterocyclic group;    T and U are independently a hydrogen atom or a substituent, or T and U form, together with ring M, an optionally substituted bicyclic ring;    D and G are independently a carbonyl group or a sulfonyl group;    ring P is optionally substituted piperidine or an optionally substituted piperazine;    B is CH or N;    ring Q is an optionally substituted monocyclic ring;    A is C, CH or N; and    J is an optionally substituted hydrocarbon group, an optionally substituted heterocyclic group or an optionally substituted amino group,    provided that when the W moiety of ring M is ═N— or —N═, U is absent,    (see Patent Document 8).    (9) A compound represented by the formula:
wherein    R1 is a hydrogen atom or a substituent; ring P is an optionally substituted 6-membered nitrogen-containing aromatic heterocycle;    ring Q is an optionally further substituted 5- to 7-membered nitrogen-containing non-aromatic heterocycle;    ring R is an optionally fused 5- to 7-membered non-aromatic ring which is optionally further substituted,    (see Patent Document 9).    (10) A compound represented by the formula:
wherein    ring E is an optionally further substituted 6-membered aromatic ring, or an optionally fused 5-membered aromatic heterocycle which is optionally further substituted;    ring P is an optionally fused non-aromatic ring which is optionally further substituted;    W is O, S, a C1-4 alkylene or NR3a wherein R3a is a hydrogen atom or a substituent;    X is O, S, SO, SO2, CO, CR1R2 or NR3b wherein R1, R2 and R3b are the same or different and each is a hydrogen atom or a substituent;    Y is an optionally substituted amino group; and    n is 0, 1, 2 or 3,    (see Patent Document 10).    (11) A compound represented by
    (see non-Patent Document 1).
However, none of the above-mentioned documents reports on the bicyclic compound of the present invention.